The human skin forms a structural and adapted barrier to the environment. It further plays an important physiological role since it provides not only protection and thermoregulation, but also has a metabolic and sensorial function and storage capacity.
It has been shown that the lipid composition of the epidermal cells within the skin changes considerably when the cells migrate to the outer surface and differentiate. The cells in the basal layer contain a complex lipid composition, with phospholipids as the major constituent In the granular layer the phospholipid content is diminished while the amount of cerebrosides (glycosylceramides), ceramides, cholesterol and cholesterol sulphate is increased as result of de novo synthesis and storage into the so-called lamellar bodies. In the outermost lipid layer of the epidermis, called the stratum corneum (horny layer) the phospholipids and cerebrosides have vanished completely. The most abundant lipids in this layer are ceramides, which mainly have been formed by enzymatic deglycosylation of cerebrosides.
The barrier function of the skin mainly is provided by the stratum corneum. The stratum corneum consists of corneocytes embedded in an extracellular matrix of multiple bilayers of lipids. The intercellular lipid phase of the stratum corneum has roughly the following composition: 40% ceramides, 25% cholesterol, 10% cholesteryl sulphate and 25% free fatty acids. As long as the “bricks and mortar”. construction of the stratum corneum is not affected, the skin is provided with both a perfect protective layer and a filter-active permeability layer.
Several categories of skin conditions or disorders are known which are characterized by an impaired lipid barrier function, further accompanied by characteristics like a deranged regulation of cell growth and differentiation (e.g. hyperproliferation and/or decreased differentiation of keratinocytes, decreased desquamation of corneocytes), an inflammatory response and/or an infectious state. In these skin conditions, the skin generally displays a rough, red, dry, chapped and/or swollen character. Typical examples of such disorders are xerosis, acne vulgaris, psoriasis, atopic dermatitis, contact dermatitis, UV-induced erythema, and the like.
Satisfactory treatment methods for these disorders presently are not available. Emollient creams and lotions may relieve part of the symptoms, but often only temporarily. Conventional anti-inflammatory creams, of which corticosteroid creams form the main part, are more effective for the treatment of certain disorders but continued use may reduce the effectiveness of the treatment and/or may give side reactions. In addition, conventional antiinflammatory as well as antimicrobial creams typically are not adapted to restore an impaired barrier function.
Ceramides are generally applied in cosmetics because of their moisture-retaining properties (see for instance Japanese patent application J61-260008).
In International patent application WO94/00127 it has been described that formulations containing specific lipid mixtures should be applied for an optimal treatment of skin disorders associated with a disrupted epidermal barrier. Said lipid mixtures comprise lipids selected from the three major classes of naturally-occurring epidermal lipids, i.e. the classes of ceramides, cholesterol and free fatty acids. However, in order to be optimally effective for skin conditions associated with inflammatory or infectious phenomena, these formulations have to be applied together with conventionally used therapeutic agents
Surprisingly, it is shown by the present invention that topical compositions comprising a combination of a free sphingoid base and a ceramide have a beneficial effect when applied on skin conditions associated with an impaired barrier function, and especially when applied on skin conditions further associated with a deranged regulation of cell growth and differentiation, inflammatory and/or infectious phenomena.